Alessandro Santin, MD, professor, Obstetrics, Gynecology, and Reproductive Sciences, Disease Aligned Research Team Leader, Gynecologic Oncology Program, co-chief, Section of Gynecologic Oncology, Yale Cancer Center, discusses the investigation of sacituzumab govitecan-hziy (Trodelvy) in patients with recurrent endometrial carcinoma overexpressing TROP2.

Investigators launched a 2-stage phase 2 clinical trial (NCT04251416) to evaluate the use of sacituzumab govitecan in this patient population. The preliminary responses from this study were presented at the 2023 ASCO Annual Meeting.

Endometrial cancer is the most common gynecological cancer in the United States, with tens of thousands new cases and deaths every year, Santin begins. When patients develop recurrent disease and become resistant to carboplatin plus paclitaxel, the current gold standard treatment approach in the recurrent- and advanced-stage disease setting, they have limited subsequent treatment options, he explains. Most of the patients evaluated in the phase 2 trial had disease that was resistant to prior chemotherapy, as well as lenvatinib (Lenvima) pluspembrolizumab (Keytruda), which is a new combination in the recurrent setting, Santin adds.

As patients with disease that is resistant to both chemotherapy and lenvatinib plus pembrolizumab have limited treatment options, the phase 2 trial investigators aimed to determine the activity of sacituzumab govitecan in this population, Santin expands. Sacituzumab govitecan is an antibody-drug conjugate that targets TROP2, a glycoprotein that is overexpressed in most endometrial cancers and conjugated through a linker with the toxic payload SN-38, which is a derivative of the topoisomerase 1 inhibitor irinotecan, he explains.

This study enrolled 21 evaluable patients in the first stage. Per the trial design, the first stage would be considered positive if at least 3 clinical responses after 21 patients enrolled role, he notes. Importantly, the response rate detected in the first 21 patient was 33.3%, Santin emphasizes. Overall, these positive findings from stage 1 supportcontinued accrual to the second stage of the study, Santin concludes.

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Alessandro Santin, MD, discusses the investigation of sacituzumab govitecan in patients with recurrent endometrial carcinoma overexpressing TROP2.


Dr Santin on the Investigation of Sacituzumab Govitecan in Endometrial Cancer

Alessandro Santin, MD, professor, Obstetrics, Gynecology, and Reproductive Sciences, Disease Aligned Research Team Leader, Gynecologic Oncology Program, Yale Cancer Center, co-chief, Section of Gynecologic Oncology, discusses the clinical activity of sacituzumab govitecan-hziy (Trodelvy) in patients with recurrent endometrial cancer who overexpress Trop-2.

Preliminary results from stage 1 of a phase 2 trial (NCT04251416) presented at the 2023 ASCO Annual Meeting showed that among 21 patients evaluable for efficacy, the objective response rate was 33.3%, including 1 (4.8%) complete response and 6 (28.5%) partial responses. Additionally, 47.6% of patients had stable disease, and 14.3% experienced progressive disease. Notably, in 20 patients evaluable for disease control, the 6-month durable disease control rate was 35.0%.

Although endometrial cancer is the most common gynecological cancer in the United States, patients who experience recurrence and become resistant to carboplatin and paclitaxel have limited treatment options, Santin begins. In this phase 2 study, patients were required to have progressed on or after treatment with platinum-based chemotherapy. Notably, many patients were resistant to previous chemotherapy, as well as lenvatinib (Lenvima) plus pembrolizumab (Keytruda), Santin explains. Sacituzumab govitecan is an antibody-drug conjugate targeting TROP-2, which is a glycoprotein that is overexpressed in a majority of endometrial cancers, Santin adds.

The study was allowed to proceed to stage 2 after stage 1 met its prespecified statistical goal of at least 3 clinical responses in the first 21 patients enrolled. Enrollment for stage 2 is ongoing, and the study will feature 50 total patients between the 2 stages, Santin concludes.

Alessandro Santin, MD, discusses the clinical activity of sacituzumab govitecan-hziy in patients with recurrent endometrial cancer who overexpress Trop-2.

Dr Santin on the Clinical Activity of Sacituzumab Govitecan in Recurrent Endometrial Cancer

Alessandro D. Santin, MD, professor of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine, discusses the impact of trastuzumab (Herceptin) in patients with uterine serous carcinoma.

Treatment with trastuzumab and chemotherapy elicited a progression-free survival (PFS) of over 50% versus chemotherapy alone in patients with HER2-positive uterine serous carcinoma. The median PFS increased from 8.0 months with carboplatin and paclitaxel to 12.6 months with the addition of trastuzumab to the same chemotherapy regimen.

Although preliminary, the results of this randomized trial demonstrate the importance of testing for HER2/neu expression in patients with endometrial cancer, says Santin. Dysregulation of HER2/neu may occur in more than one-fourth of the tumors, and HER2/neu overexpression has been reported in as many as 60% of patients with uterine serous carcinoma. The overexpression of HER2/neu would give a patient the opportunity to be treated with trastuzumab in addition to chemotherapy.

Alessandro D. Santin, MD, professor of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine, discusses the impact of trastuzumab (Herceptin) in patients with uterine serous carcinoma.
 

Dr. Santin on Impact of Trastuzumab in Uterine Serous Carcinoma

Alessandro D. Santin, MD, professor of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine, discusses the rationale for trastuzumab (Herceptin) in the treatment of patients with uterine serous carcinoma.

A small randomized study showed that patients with HER2-positive uterine serous carcinoma had a greater than 50% improvement in progression-free survival (PFS) when treated with trastuzumab and chemotherapy versus chemotherapy alone. A preliminary survival analysis showed a trend in favor of the trastuzumab arm, as the median PFS increased from 8.0 months with carboplatin and paclitaxel to 12.6 months with the addition of trastuzumab to the same chemotherapy regimen.

About 30% of patients with uterine serous carcinoma overexpressed HER2/neu, says Santin. This overexpression may qualify a patient for treatment with trastuzumab.

Alessandro D. Santin, MD, professor of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine, discusses the rationale for trastuzumab (Herceptin) in the treatment of patients with uterine serous carcinoma.
 

Alessandro D. Santin, MD

Articles

Dr Santin on the Investigation of Sacituzumab Govitecan in Endometrial Cancer

Dr Santin on the Clinical Activity of Sacituzumab Govitecan in Recurrent Endometrial Cancer

Dr. Santin on Impact of Trastuzumab in Uterine Serous Carcinoma

Dr. Santin on Rationale for Trastuzumab in Uterine Serous Carcinoma